A comparative ultrastructural and molecular biological study on Chlamydia psittaci infection in alpha-1 antitrypsin deficiency and non-alpha-1 antitrypsin deficiency emphysema versus lung tissue of patients with hamartochondroma

BACKGROUND: Chlamydiales are familiar causes of acute and chronic infections in humans and animals. Human pulmonary emphysema is a component of chronic obstructive pulmonary disease (COPD) and a condition in which chronic inflammation manifested as bronchiolitis and intra-alveolar accumulation of macrophages is common. It is generally presumed to be of infectious origin. Previous investigations based on serology and immunohistochemistry indicated Chlamydophila pneumoniae infection in cases of COPD. Furthermore, immunofluorescence with genus-specific antibodies and electron microscopy suggested involvement of chlamydial infection in most cases of pulmonary emphysema, but these findings could not be verified by PCR. Therefore, we examined the possibility of other chlamydial species being present in these patients. METHODS: Tissue samples from patients having undergone lung volume reduction surgery for advanced alpha-1 antitrypsin deficiency (AATD, n = 6) or non-alpha-1 antitrypsin deficiency emphysema (n = 34) or wedge resection for hamartochondroma (n = 14) were examined by transmission electron microscopy and PCR. RESULTS: In all cases of AATD and 79.4% of non-AATD, persistent chlamydial infection was detected by ultrastructural examination. Intra-alveolar accumulation of macrophages and acute as well as chronic bronchiolitis were seen in all positive cases. The presence of Chlamydia psittaci was demonstrated by PCR in lung tissue of 66.7% AATD vs. 29.0% non-AATD emphysema patients. Partial DNA sequencing of four positive samples confirmed the identity of the agent as Chlamydophila psittaci. In contrast, Chlamydophila pneumoniae was detected only in one AATD patient. Lung tissue of the control group of non-smokers with hamartochondroma was completely negative for chlamydial bodies by TEM or chlamydial DNA by PCR. CONCLUSIONS: These data indicate a role of Chlamydophila psittaci in pulmonary emphysema by linking this chronic inflammatory process to a chronic infectious condition. This raises interesting questions on pathogenesis and source of infection

Daily variations of ELF data observed by a low-altitude satellite

International audienceData from a low-orbiting satellite with a quasipolar orbit have been studied to determine if man-made waves, such as the Power Line Harmonic Radiations (PLHR), can affect the intensity of the ELF waves observed in the ionosphere. The signals coming from two electric components were processed with a system of 6 filters (from 10 Hz up to 1000 Hz), and recorded on-board all around the Earth. Most ELF waves derive from electrostatic turbulence. It is shown that the signal recorded by the electric component that is parallel to the Earth's magnetic field has a modulation depending of the days of the week. The amplitude is maximum on Monday and decreases until Saturday. The largest difference between Monday and Saturday (93%) occurs with the filter centered around 72 Hz. The interpretation of the experimental results supposes that the intensity of the ELF waves is connected to the PLHR influence on the ionospheric plasma. A theory is presented to explain this variation: the PLHR emitted from the ground during weekdays are different from those of the weekend, not 0nly because power consumption is lower, but also because the ground configuration of their sources is changed. 1955, 9600 TWh in 1985. The propagation of the PLHR through the magnetosphere was first observed by Helliwell et al. [1975], but only on the ground at a conjugate point of an industrialized region. Similar 6bservations on the ground were made from different places by Matthews and Yearby [1981] and Kimura et al. [1987]. Rare and weak PLHR emissions were observed onboard the satellites ISEE-1 [Bell et al., 1982] above North America and AUREOL-3 [Berthelier eta!., 1982] above Western Europe. However, studies with the low-altitud

Predictors and outcomes of early coronary angiography in patients with prior coronary artery bypass surgery presenting with non-ST elevation myocardial infarction.

INTRODUCTION: The best strategy in patients with prior coronary artery bypass graft surgery (CABG) who present with non-ST elevation myocardial infarction (NSTEMI) remains less well defined. We compare the characteristics, therapeutic interventions and outcomes of patients with prior CABG presenting with NSTEMI. METHODS: All patients who presented to our hospital during 2007-2012 with available electronic records were analysed retrospectively. Outcomes were compared between patients who underwent coronary angiography or percutaneous coronary intervention (PCI) versus those who were treated medically. RESULTS: A total of 117 patients were analysed. Of that, 79 patients were managed medically while 38 underwent early angiography, of which only 11 (9.5%) received PCI. Patients treated medically (did not undergo angiography) were older (74±10 vs70±8; p=0.05). ECG changes were the only independent predictor for early angiography (OR 0.4, 95% CI 0.15 to 0.99; p=0.05) while recurrent chest pain (OR 0.2, 95% CI 0.05 to 0.97; p=0.05) predicted PCI on multivariate analysis. The PCI group had higher Global Registry of Acute Cardiac Events (GRACE) score (176±29 vs 150±31; p=0.01). No significant difference was found in readmission rates, morbidity (unstable angina pectoris, NSTEMI, ST elevation myocardial infarction (STEMI), or combination) or mortality at 12 months between the groups who underwent angiography, PCI, or treated medically on univariate and multivariate analysis. CONCLUSIONS: The opportunity to intervene in prior CABG patients presenting with NSTEMI is often low. Initial medical management may be a reasonable option in carefully selected patients particularly in the absence of ongoing symptoms, ECG changes or very high GRACE scores. Further studies are required to evaluate the safety of non-invasive strategies in managing this population

Development of a severity score for CRPS

The clinical diagnosis of Complex Regional Pain Syndrome (CRPS) is a dichotomous (yes/no) categorization necessary for clinical decision-making. However, such dichotomous diagnostic categories do not convey an individual's subtle and temporal gradations in severity of the condition, and have poor statistical power when used as an outcome measure in research. This study evaluated the validity and potential utility of a continuous type score to index severity of CRPS. Psychometric and medical evaluations were conducted in 114 CRPS patients and 41 non-CRPS neuropathic pain patients. Based on the presence/absence of 17 clinically-assessed signs and symptoms of CRPS, an overall CRPS Severity Score (CSS) was derived. The CSS discriminated well between CRPS and non-CRPS patients (p < .001), and displayed strong associations with dichotomous CRPS diagnoses using both IASP diagnostic criteria (Eta = 0.69) and proposed revised criteria (Eta = 0.77-0.88). Higher CSS was associated with significantly higher clinical pain intensity, distress, and functional impairments, as well as greater bilateral temperature asymmetry and thermal perception abnormalities (p's < .05). In an archival prospective dataset, increases in anxiety and depression from pre-surgical baseline to 4 weeks post-knee arthroplasty were found to predict significantly higher CSS at 6- and 12-month follow-up (p's < .05). Results indicate the CSS corresponds with and complements currently accepted dichotomous diagnostic criteria for CRPS, and support its validity as an index of CRPS severity. Its utility as an outcome measure in research studies is also suggested, with potential statistical advantages over dichotomous diagnostic criteria. (C) 2010 Published by Elsevier B.V. on behalf of International Association for the Study of Pain.Neurological Motor Disorder

Vedolizumab for ulcerative colitis: Real world outcomes from a multicenter observational cohort of Australia and Oxford

Background: Vedolizumab (VDZ), a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis (UC) patients. Aim: To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving remission. Methods: A retrospective review of Australian and Oxford, United Kingdom data for UC patients. Clinical response at 3 mo, endoscopic remission at 6 mo and clinical remission at 3, 6 and 12 mo were assessed. Cox regression models and Kaplan Meier curves were performed to assess the time to remission, time to failure and the covariates influencing them. Safety outcomes were recorded. Results: Three hundred and three UC patients from 14 centres in Australia and United Kingdom, [60% n = 182, anti-TNF naïve] were included. The clinical response was 79% at 3 mo with more Australian patients achieving clinical response compared to Oxford (83% vs 70% P = 0.01). Clinical remission for all patients was 56%, 62% and 60% at 3, 6 and 12 mo respectively. Anti-TNF naive patients were more likely to achieve remission than exposed patients at all the time points (3 mo 66% vs 40% P \u3c 0.001, 6 mo 73% vs 46% P \u3c 0.001, 12 mo 66% vs 51% P = 0.03). More Australian patients achieved endoscopic remission at 6 mo compared to Oxford (69% vs 43% P = 0.01). On multi-variate analysis, anti-TNF naïve patients were 1.8 (95%CI: 1.3-2.3) times more likely to achieve remission than anti-TNF exposed (P \u3c 0.001). 32 patients (11%) had colectomy by 12 mo. Conclusion: VDZ was safe and effective with 60% of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome

P571 Vedolizumab (VDZ) real-world outcomes in ulcerative colitis (UC)

Background: In GEMINI 1, UC response to vedolizumab (VDZ) was 47% at Week 6 and 42% by Week 52. Our aim was to assess real-life outcomes for VDZ in UC. Methods: Data collected at 12 Australian (Aus), 1 UK and 2 Hong Kong (HK) centres, assessed response to VDZ at 3, 6, and 12 months using the Mayo Clinic Score (MCS, Aus/HK) or SCCAI and UCEIS (UK). Results: Two hundred and ninety-three patients (53% male, median age 38 years, 196 Aus, 93 UK, 4 HK) were assessed with similar age, disease location and duration allowing combining of data. Median MCS pre VDZ was 8 (range 2–12, n = 152) and Mayo endoscopy subscore 2 of 3 (Aus, HK). Median SCCAI was 8 (range 0–13, n = 87) and UCEIS 5 of 8 (UK). VDZ was the first biological agent in 170 of 293 (58%), prior anti-TNF use occurred in 123 [reason for switching: primary non-response (PNR) n = 46, loss of response (LOR) n = 62, side-effects (SE) n = 15; two patients with side-effects were in remission and not included for analysis]. At VDZ start, 61% taking steroids and 56% immunomodulation (IM). Response rates at 3 months: 220 of 279 (79%) overall responded, TNF-naïve 134 of 163 (82%), TNF-exposed 86 of 116 (74% p = NS). Remission rates at 3 months: 155 of 279 (55%) in clinical remission, TNF-naïve 110 of 163 (67%), TNF-exposed 45 of 116 (39%, p = 0.01). 60 of 132 (45%) patients in remission were on IM and 49 of 101 (49%) if not (NS). Six months: Overall 144 of 235 (61%) in clinical remission, TNF-naïve 97 of 131 (74%), TNF-exposed 47 of 104 (45%, p = 0.03), and 60 of 124 (48%) in endoscopic remission (MES = 0 or 1). Steroids were ceased in 61 of 136 (45%) if in remission and 23 of 85 (27%) if not (p = 0.08). 39% (49 of 125) patients in remission were on IM and 29% (24 of 82) if not (NS). 12 months: Overall 117 of 196 (60%) were in remission, TNF-naïve 72 of 106 (68%), TNF-exposed 45 of 90 (50%, NS). No significant difference in remission rates seen between PNR, LOR, or anti-TNF naïve patients. Steroids ceased in 55 of 110 (50%) if in remission and 6 of 80 (8%) if not (p ≺ 0.001). Thirty-seven of 104 (36%) patients in remission were on IM and 13 of 78 (17%, p = 0.03) if not. Those in remission at 3 and 6 months, 90% (74 of 82) and 92% (96 of 104), respectively maintained remission. Smoking status did not affect response to VDZ. Colectomy occurred in 33 of 293 (11%). Adverse events occurred in 20 of 293 (7%); 2 were serious (Klebsiella sepsis and hemophagocytic syndrome). Conclusions: VDZ induced remission in 55% at 3 months and 61% at 6 months with &gt;90% maintaining remission at 12 months. VDZ use continued for 12 months in 71% (139 of 196) with 61% in remission. Steroids were withdrawn in 50% patients in remission at 12 months. IMs might increase remission rates at 12 months. VDZ was initially more effective in anti-TNF naïve patients but differences were lost at 12 months suggesting patience may be needed in anti-TNF-exposed patients